ABCA4 gene mutations in Japanese patients with Stargardt disease and retinitis pigmentosa.

PURPOSE: To evaluate photoreceptor cell-specific adenosine triphosphate (ATP)-binding cassette transporter (ABCA4) gene mutations in Japanese patients with Stargardt disease (STGD) and the correlation of these mutations to clinical phenotypes. METHODS: Serum was obtained from 10 unrelated Japanese patients with STGD and 96 unrelated Japanese patients with autosomal recessive retinitis pigmentosa (arRP). All 50 ABCA4 gene exons of the patients with STGD were screened for mutations by a combination of single-strand conformation polymorphism analysis and polymerase chain reaction (PCR) direct-sequencing techniques. By restriction enzyme digestion, primer extension analysis, and PCR direct sequencing techniques, the patients with arRP were screened for three segregated, presumably null ABCA4 gene mutations observed in Japanese patients with STGD. RESULTS: Three novel, presumably null mutations of the ABCA4 gene, IVS7-45_952delinsTCTGACC, IVS12+2T-->G, and 1894delA, were identified. The Arg2149stop mutation that had been found in a white patient with STGD in a prior study was also found in a Japanese patient. Two arRP-affected siblings and two unrelated patients with STGD were found to be homozygous for the same IVS12+2T-->G mutation, and three other arRP-affected siblings were carriers of the IVS12+2T-->G mutation and/or the IVS7-45_952delinsTCTGACC mutation. These three siblings with arRP showed only atrophic degeneration in the macula early after the onset of the disease, and STGD had been diagnosed. CONCLUSIONS: Three novel ABCA4 gene mutations were identified in Japanese patients with STGD and arRP. Mutations in the ABCA4 gene can cause panretinal degeneration that changes its clinical appearance from STGD to arRP over time.

Evaluation of residual retinal function by pupillary constrictions and phosphenes using transcorneal electrical stimulation in patients with retinal degeneration.

BACKGROUND: To evaluate inner-retinal function by pupillary constrictions and phosphenes evoked by transcorneal electrical stimulation (TES) in patients with hereditary retinal degeneration. METHODS: Consecutive 20 eyes of 20 patients (16 with retinitis pigmentosa (RP); and four with cone-rod dystrophy (CRD)) whose visual acuity was equal to or worse than 20/2000 at Osaka University Hospital and eight eyes of eight healthy subjects were enrolled. TES was performed on with a contact lens stimulating electrode. The electrically evoked pupillary response (EEPR) was recorded by a pupillometer, and the phosphenes by the subjective responses. Three electrical current thresholds were determined: T1, threshold current for initial phosphene; T2, threshold for eliciting a phosphene extending into the central field; and P, threshold for a relative pupillary constriction > or = 3%. The EEPR and phosphene thresholds were compared with the visual acuity or the visual field. RESULTS: All T1, T2 and P were significantly higher in patients than in normals (Mann-Whitney, P<0.001). Both T1 and T2 were not correlated with visual acuity but depended on the area and location of the residual visual field. T1 and T2 in RP eyes with a EEPR was significantly lower than that in RP eyes without an EEPR. During TES, all subjects and patients had no pain, and no complications except for a slight corneal superficial punctuate keratopathy. CONCLUSIONS: The safety and the efficacy of TES to estimate the residual inner-retinal function in patients with retinal degeneration indicate that TES can be used as one of the most important test to select candidates for retinal prostheses.

Effect of simultaneous oblique muscle surgery in foveal translocation by 360 degrees retinotomy.

PURPOSE: To assess the effect of simultaneous oblique muscle surgery during foveal translocation surgery with 360 degrees retinotomy in patients with neovascular maculopathy. METHODS: Foveal translocation with 360 degrees retinotomy was performed on 31 eyes of 31 patients with neovascular maculopathy (21 with age-related macular degeneration 9 with myopic neovascular maculopathy, and 1 with idiopathic neovascular maculopathy). All eyes had simultaneous torsional muscle surgery with recession of the superior oblique muscle and tucking of the inferior oblique muscle. Visual acuity, binocular vision, and degree of cyclotorsion were assessed pre- and postoperatively. The angles of retinal and global rotation, distance of foveal shift, and surgical complications were also investigated. RESULTS: With a mean postoperative follow-up of 10.0 months, vision improved (>0.2 log MAR units) in 13 eyes, was unchanged in 9 eyes, and worsened (>0.2 log MAR units) in 9 eyes. Ten of 31 eyes (32%) had a final visual acuity of 20/50 or better. Eleven patients had binocular fusion, 13 patients showed suppression, and 7 patients developed diplopia that was managed by spectacles with prisms or by secondary muscle surgery. The mean retinal and global rotations were 30.3 degrees and 23.7 degrees, respectively. The average size of the choroidal neovascular membrane was 1.3 disc diameters (DD), while the average shift of the fovea was 1.5 DD. After the primary surgery, six eyes developed retinal detachment, two eyes macular hole, and three eyes proliferative vitreoretinopathy. These complications were successfully managed by additional surgery. CONCLUSION: Foveal translocation with 360 degrees retinotomy is effective in restoring vision in 40% of patients with neovascular maculopathy. Simultaneous oblique muscle surgery was effective in rotating the globe by about 20 degrees, corresponding to to a foveal shift of 1.5 DD. While the development of torsional diplopia is generally prevented by simultaneous oblique muscle surgery, the relatively high incidence of surgical complications with this procedure should be taken into account.